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基因法必成奇

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Otherwise they might end up a niche treatment for a small number of patients in rich countries

否，它最可能成富裕家中，少病患的利基法。

In 2018, when he was 13, Ethan Ralston’s eyesight started to get blurry. The diagnosis was devastating. He had been born with Leber Hereditary Optic Neuropathy (LHON), a rare genetic disorder that eats away at the cells of the optic nerve until it causes blindness.

於2018年，Ethan Ralston 13，其力始模糊。果是具性的。他出生，患有雷伯氏性神病(LHON)，是一逐神胞，最後致失明的罕疾病。

Given that America and Europe between them see just 800 cases of lhon a year young Mr Ralston was very unlucky. In another way, though, he could be counted fortunate. GenSight, a French biotech company, had for years been working on a gene therapy for lhon.

已知，在美洲之，每年800起LHON病例，年的Ralston 先生非常不幸。不，另一方面，他或算是幸的。法GenSight生物技公司，多年一直致力於一，供LHON使用的基因法。

The condition is caused by a mutation in a gene called nd4 which causes the body’s cells to make a faulty protein. The therapy, called Lumevoq, sought to resolve the problem by adding the canonical version of nd4 to cells in the retina and optic nerve. By 2018 Lumevoq was in clinical trials. Shortly after his diagnosis Mr Ralston was treated with it.

疾病是由一，被nd4之基因的突，致身胞生有缺陷蛋白所引起。被Lumevoq的法，藉由形式的nd4添加到，膜及神的胞中，求解此。到2018年，Lumevoq法入了床段。在Ralston先生的出後不久，他接受了以此法的治。

Today his eyesight has almost returned to normal. He can work on a computer, drive a car, go bowling with his friends. He would seem to be cured.

目前，其力乎已恢正常。他能在上工作、及朋友打保球。他似乎竟被治。

Such stories are becoming increasingly common. In the 2010s a whole year might see only one new gene-therapy approval from regulators. This August alone saw two, one for beta thalassaemia and one for haemophilia a, both diseases of the blood.此故事得日益普遍。於2010年代，一整年可能有一新的基因法，得管批准。今年(2022年)8月就有，一供β型地中海血，一供a型血友病使用。皆血液疾病。

The Alliance for Regenerative Medicine, an international industry group for cell and gene therapies, says that 1,369 groups are developing such treatments and just over 2,000 clinical trials are under way.

再生盟(一胞暨基因治行)表示，有1369正在此治法，且2千多床正在行。

Most of those in their earliest stages and may well progress no further: many are cell therapies which do not require changes to the patient’s genes. Still, according to scientists from the Centre for Biomedical Innovation in Cambridge, Massachusetts, there are enough trials under way that 40-50 new gene therapies could be approved for clinical use by 2030.

那些大多於最初期段，因此恐怕可能不有更一步展：多是需改病患基因的胞法。管如此，根自美塞州市，生物新中心科家的法，有多正行中的，到2030 年，40-50新的基因法，可能得批准供床使用。

A lot of these will be used in the fight against cancer. Removing from the body some of the T-cells which the immune system uses to fight cancer, giving them a gene that lets them recognize a cancer-specific trait and putting them back is the basis of CAR-t therapies, one of the hottest approaches around.

此些很多被用於抗癌症。身移除一些，免疫系用抗癌症的T胞，予它一，使其癌特性特徵的基因，它放回去，是嵌合抗原受(CAR：Chimeric Antigen Receptor )-T胞法的基。是泛被用的最方法之一。

But there will also be lots that tackle inherited diseases. There are clear signs that this surge has begun. Janet Lambert, the boss of the Alliance for Regenerative Medicine, anticipates that Europe and America will see a record number of such gene therapies approved this year (see table).

不，也有很多解疾病的方法。有多激增已始的明象。再生盟的，Janet Lambert期，今年洲及美看到，量的此基因法得批准(上表)。

In a world where saying that something is in some person or other entity’s DNA has become a shorthand for seeing it as part of their very essence, dealing with inherited diseases this way looks truly revolutionary. It is “one of the most compelling concepts in modern medicine” as a recent review paper put it.

在一，某物存在於某人或其他之DNA中的世界，已成它，其本之一部分的速法。以方式理性疾病看起，具革命性。如同最近一篇的文所述，它是“代中，最引人注目的概念之一”。

The ability to provide someone with a single treatment that will alleviate a terrible condition for a decade or more—perhaps even for life—is an intervention without any obvious parallel.

能某人提供，以一能解可怕疾病，十年或更(或甚至生)之一法的能力，是一有任何明行的干。

But it comes with a number of challenges. The techniques being used still carry risks. The therapies themselves are enormously expensive, not just because of the research required to develop them—that is expensive all across the biotech world—but because the cost of making them is particularly hih.

不，生多挑。正被使用的多技仍然具有。此些法本身是非常昂的，不只是因它所需的研究(在整生物技域中，那是昂的)，而且因作它的成本特高昂。

What is more, some may face stiff competition from other approaches, some of them equally novel. These may allow some of the condition’s gene therapy seeks to fix to be treated in cheaper ways.

更重要的是，有些方法可能面，自其他方法的激烈，其中有些同新。此些方法可能使基因法理的某些疾病得以，以便宜的方式被治。

This raises the possibility that, impressive as they are, gene therapies might be relegated to a niche treating a small number of patients in rich countries. That would be a poor outlook for millions around the world who suffer from more common genetic diseases, such as sickle-cell disease, and other conditions.

管基因法令人印象深刻，不引了，它可能被置於，治富裕家中少病患之利基市的可能性。世界各地百罹患常疾病(如胞症及其他疾病)的人而言，那是一不好的前景。

It could also scupper the chances of gene therapy moving beyond the realm of single-gene disorders to tackle more complex conditions. For many more people to experience the sort of benefits that have changed Mr Ralston’s prospects, the ability to produce miracles will not be enough.

也可能破，基因法超越基因疾病，以解更疾病的。了更多的人，到改斯的前景的益，造奇的能力是不的。

They have to be produced affordably in ways that can be adapted to conditions far removed from the elite hospitals where trials typically take place today.

它必以能被用於，目前通常行之精英院的件方式，廉地被生。

To design a gene therapy, you need a gene you want to add to the patient’s cells and a way of getting it into them. Finding the first is, in principle, easy: thousands of diseases, most of the worst thankfully rare, come about because of a garbled copy of a single gene.

要一基因法，需要一想要添加到病患胞中的基因，及一其入胞中的方法。原上，找到第一是容易的：天地，千疾病中，最糟糕的大多是罕的，因一基因生的。

That means they might in principle be alleviated by the addition of the normal version. The second is normally the job of a modified virus that can no longer reproduce but that can get a new gene into its target cells: a viral “vector”.

那意味著，原上藉由添加正常形式基因，它能被解。第二通常是修之病毒的工作，它不再能繁殖，能新基因入其靶胞中：也就是，一病毒“”。

Sometimes cells are taken out of the body, transformed by a vector and put back in, as they are in car-t cancer therapies. Zynteglo, a gene therapy for beta thalassaemia made by bluebird bio, works this way.

有後，胞被取出，由化放回，如同它在嵌合抗原受(CAR：Chimeric Antigen Receptor )-T胞的癌症法中一。由(位於美塞州市，一家重疾病及癌症基因法的生物技公司)bluebird bio公司所造，供β型地中海血使用的Zynteglo基因法，是以此方式起作用。

On August 17th it became the third gene therapy for an inherited disease to be approved by America’s Food and Drug Administration (FDA). In other cases the vector does its work inside the body. Lumevoq—approved by the European Medicines Agency (EMA) in 2021, but not yet by the FDA—was injected directly into Mr Ralston’s eyes.

於2022年8月17日，它成第三，得美食品暨物管理局(FDA)批准，供一性疾病使用的基因法。在其他例中，於起作用。於2021年由洲品管理局(EMA)批准，不FDA尚未批准的Lumevoq法，被直接注射到Ralston先生的眼睛。

The first gene-therapy trial, which treated a single child with a specific and severe immunodeficiency called ADA-SCID, got under way in 1990. It did not lead quickly to a commercial product (a different gene therapy for ada-scid, Strimvelis, was eventually approved in 2016) but it paved the way for a number of successors.

治了一位罹患特定且重免疫缺陷之童，被腺苷氨酶(ADA：Adenosine deaminase)-重合型免疫缺陷症(SCID：severe combined immunodeficiency)的首度基因法，於1990年始。有迅速致成商品(一供ADA-SCID使用的不同基因法，Strimvelis法最於2016年得批准)，不多後者了路。

Unfortunately in 1999 the nascent field was rocked by the death of Jesse Gelsinger, an 18-year-old, four days after he had been given a gene intended to fix his inherited inability to metabolize ammonia.

不幸的是，於1999年，18的Jesse Gelsinger，在他被施予一，旨在修其上代氨之能力的基因，四天後死亡，震了新域。

His death was caused by his immune system’s response to the adenovirus used as a vector. That knowledge drove the hunt for safer vectors; James Wilson, a gene-therapy pioneer at the University of Pennsylvania, where the trial during which Mr Gelsinger died was based, uncovered the potential of adeno-associated viruses (AAV).

他的死亡是由其免疫系，使用作之腺病毒的反所引起。那消息了找更安全的；在美州大，以Gelsinger先生死亡做基的期，基因法先James Wilson揭露了，腺相病毒(AAV)的在性。

These are widespread in humans and are not known to cause any sort of disease; they provoke little or no immune response. That is one of the reasons that they have also been taken up by vaccine-makers. The Oxford AstraZeneca covid-19 vaccine works in this way, using an aav to put dna describing a telltale viral protein into the body’s cells.

於人中，此些是的，且不知道引起任何型疾病。它很少或根本有引起免疫反。那是疫苗造商，也一直用它的原因之一。英牛津阿斯利康2019冠病毒症(COVID-19：Coronavirus Disease-19)疫苗，以方式起作用。也就是，使用一AAV，描述一露秘密之病毒蛋白的DNA，置入人胞中。

For gene therapies, AAVs have the big advantage of coming in more than 100 different flavours, or serotypes, each of which has different preferences when it comes to which sorts of cell to infect. Vectors derived from AAVs are able to home in on specific tissues such as the optic nerve, or the central nervous system, or the muscles.

就基因法而言，AAVs具有能得百不同特(flavours)，也就是血清型的。每一在感染哪胞，有其不同的偏好。源自AAVs的能向特定，如神、中神系或肌肉。

However, AAV-based vectors are not without problems. A recent analysis of almost 150 gene-therapy trials using them found that 35% had seen “serious adverse events”, including brain-imaging findings of “uncertain significance”. Large doses of the vector have also been linked to safety concerns. In 2018 Dr Wilson warned that high doses of AAV caused life-threatening toxicity in piglets and monkeys.

然而，以AAV基的非。最近一有近150件，使用基因治之行的分析，35%已出“重不良事件”，包括“意不明”的大成像分析果。大量的也已安全被在一起。於2018年，Wilson博士警告，高量的AAV於小及猴子中，致威生命的毒性。

At the same time he resigned from the scientific advisory board of Solid Biosciences, a gene-therapy firm focused on muscular dystrophy, citing emerging concerns about the possible risks of too much AAV.

在此同，提出出有多AAV之可能的。他去了Solid Biosciences(一家美生命科公司，著重於革性治方法，以改善杜氏肌不良症(Duchenne)病患者生活的基因法公司)公司科委的。

The firm says his resignation was due to findings in experiments that were unrelated to its work. Nonetheless its regulatory filings acknowledge that the high dosing requirements for the therapy it is developing may increase the risk of side-effects.

In August Novartis, a Swiss drug company, reported two liver-related deaths in children who were treated with its gene therapy for spinal muscular atrophy (SMA).

公司表示，他的是由於，在其工作之中的研究果。管如此，其管理的文件，此正中之法的高量需求，可能增加副作用的。於(2022年)8月，瑞士Novartis公司告了，起童接受其供脊髓性肌萎症(SMA)使用之基因法，肝有的死亡。

Trials of a therapy being developed by Astellas, a Japanese drug company, for a rare muscle disease called X-linked myotubular myopathy produced some spectacular results, but also saw three children die with sepsis and gastrointestinal bleeding as a consequence of liver failure and a fourth from other liver-related complications.

一正由日本Astellas公司，供一被X-肌管肌症(X-LMTM)使用的多，生了一些人的果。不，也了三名童，因肝功能衰竭死於血症及消化道出血，第四名童死於其他肝相的症。

Bernhardt Zeiher, who is about to retire as Astellas’s head of development, recently told Endpoints, an online publication, the company thinks the deaths were caused by a combination of a reaction to the AAV vector used and an underlying risk of liver disease. The transformational nature of the therapy itself, he added, means that the firm is committed to finding a way forward in the field.

即退休之Astellas公司的管，Bernhardt Zeiher最近告《Endpoints》(一路出版物)，公司，些死亡是由，使用之AAV的反在的肝疾病所共同致。他附言，法本身的化本，意味著公司注於，在域找一前的道路。

There have also been concerns over the potential for some vectors to trigger cancers in the long term. “You are giving [patients] quadrillions of vector particles,” says David Lillicrap, a professor at Queen’s University in Kingston, Ontario, who works on haemophilia. “A very, very small percentage are going to get into the host genome [in] susceptible areas.”

看，於某些引癌症的可能性，也一直有多。加拿大安大略省金斯敦市，皇后大致力於血友病的教授，David Lillicrap宣：「你正施予[病患]10¹⁵粒子。非常、非常小的一部分，[於]易感域，入宿主基因中。」

In 2020 a patient who was being treated for ADA-SCID with Strimvelis, which uses an RNA-based retrovirus as a vector, developed leukaemia. Orchard Therapeutics, the company marketing Strimvelis, has said it “may be attributable” to the way the gene integrated itself into the genome.

於2020年，一名接受使用，以RNA之逆病毒作的Strimvelis法，治腺苷氨酶-重合型免疫缺陷症(ADA-SCID)的病患，罹患上白血病。售Strimvelis法的Orchard Therapeutics公司表示，“或可因於”，基因自身整合到基因中的方式。

Nicole Paulk of the University of California, San Francisco, says that despite some worrying headlines the AAV vector is “extraordinarily safe”. She says it has been or is being used in over 250 clinical trials with tens of thousands of patients, and that, compared with cancer drugs, it has been remarkably well tolerated.

美加州大金山分校的Nicole Paulk表示，管有一些令人的新，不AAV是“非常安全”。她表示，它已或正被使用於，具有名病患的250多床中。而且，抗癌物相下，其被耐受性一直十分著。

Given that patients can have terrible experiences with cancer drugs that might not seem reassuring. But there are two other factors to bear in mind. One is that the patients in gene-therapy trials are often very unwell to begin with, and may come into them on other quite arduous treatment regimes. Adverse events are to be expected. More importantly, they may have little if anything by way of other options.

於病患在使用癌症物，有似乎不可能令人放心的可怕。不，切有其他因素。一是，於基因法中的病患，通常一始就非常不，而且可能在其他相的治中，致此些不。不良事件是可以料的。更重要的是，真正起的，他可能少有由其他的。

Karen ignet-Aiach is the founder and boss of Lysogene, a French gene-therapy firm which concentrates on errors in the central nervous system. Firms like hers, she says, have to battle to make sure that regulatory agencies stick to the principle that the risks attached to a treatment have to be balanced against the benefits that a therapy for something lethal and untreatable could bring.

Karen Pignet-Aiach是法注於，中神系出之基因法，Lysogene公司的始人兼老。她表示，多像其公司的公司，必努力保管理所持，治附的，必治致命及法治的疾病，可能之益相平衡的原。

In 2020 Lysogene had to deal with the difficult death of a child during a trial, putting a temporary halt to its clinical work. Ms Pignet-Aiach says the death may have been caused by medication given outside the trial but that there was no link with the treatment that was actually being investigated.

於2020年，Lysogene公司不得不，在一次期，理一名童解的死亡，而停止其床研究。Pignet-Aiach 女士表示，童的死亡可能是因之外，被施予的物所致。除非被查研究的治有性。

As to the possible benefits, when she says “Our patients have nothing [else] available” she knows what she is talking about: she lost a daughter to Sanfilippo syndrome, one of the disorders the company is tackling.

至於可能的益，她表示，“我的病患有[其他]可使用”，她知道自己在什：她因Sanfilippo徵候群(也黏多醣症III型 (MPS III)，是一罕的常染色性溶酶症，主要影大及脊髓)失去了一女。是公司正著手付的疾病之一。

Hold-ups when patients die are understandable, but they increase the cost, and risk, of developing these medicines. And there are other hurdles. Because no one yet knows how many years of duty can be expected from gene therapies, long-term studies are needed; regulators will often insist on them continuing after approval.

病患死亡，造成的延是可以理解的。不，它增加了些物的成本及。因至今人知，能期多少自基因法的任年。因此，需要多期的研究；管通常持，它在批准後持研究。

Because the conditions involved are often progressive and untreatable by other means there are real ethical concerns about randomising trials, something often seen as the best way to clear-cut results.

因，此些涉及的通常是的，且法藉由其他方法治。因此，有通常被得明果的最佳方式，也就是化的，有多真正的理。

These problems go some way to explaining the remarkable price of the therapies which make it to market—and which, because of those prices, sometimes leave it soon afterwards.

p class="MsoNormal" style="mso-line-height-alt: 0pt; layout-grid-mode: char;">在某程度上，此些解了，使些法入市的人格。由於那些法的格，因此其後市有很快放它。

When Glybera, a therapy developed by uniQure, a Dutch company, to address an error in the way fat is processed in a particularly rare condition, got the nod from the EMA in 2012 it became the first gene therapy to be approved by a stringent regulator. It also became the first medical treatment with a price tag of $1m.

一，由荷uniQure公司的Glybera法，在特罕情下，面理脂肪之方式中的差，於2012得了洲物管理局(EMA：European Medicines Agency)首肯，成第一由格管批准的基因法。它也成第一具有格，1百美元的物治法。

The first approval by the FDA, in 2017, was for Luxturna, a gene therapy to prevent another form of progressive vision loss. Roche, a big-pharma company, priced it at $425,000. Per eye. In 2019 Zolgensma, Novatis’s treatment for SMA, went on sale at $2.1m.

於2017，第一由美食品暨物管理局批准的是Luxturna法。是一防止另一形式之性力失的基因法。大型的氏公司其定，每眼睛425千美元。於2019年，Novatis公司治脊髓性肌萎症的Zolgensma法，以210美元的格上市。

Last year the mother of a baby being treated with Zolgensma remarked that everyone who touched the drug, or was around it, had to be trained to handle it: it was “like carrying gold”. Libmeldy, approved by the ema in 2020 to treat a disorder which degrades the nervous system, costs £2.8m ($3.3m) a dose.

去年(2021年)，一位正接受使用Zolgensma法治的母述，每接物，或在其周遭的人，必接受培以理它：“如同金”。於2020年，由洲物管理局批准，以治一使神系退化之疾病的Libmeldy法，每花280英(330美元)。

Pharmaceutical companies do not discuss the basis of drugs’ prices. In America the approach is typically taken to be an assessment of what the market will bear, which has led to an environment accustomed to high prices. The problem with gene therapies is that the price being charged seems in some cases well beyond what the market will bear.

公司不品格的基。在美，方法通常被，是市所能承受的估。已致一，於高格的境。有基因法的是，在某些例中，收取的格似乎超出市所能承受。

Take Glybera, the first-approved therapy. Only a single dose was ever sold. It has been withdrawn from the European market. According to Stat, another online publication, after the ema approved Zynteglo in 2019 bluebird bio offered it in Germany for $1.8m a treatment; Germany offered to pay $950,000 in cases where it worked, $790,000 when it didn’t.

以第一批准的Glybera法例。至今，才售出一。它已被撤洲市。根另一路出版物Stat的法，在2019年，洲物管理局批准Zynteglo法之後，美bluebird bio公司，在德提供法，一次治180美元；德提供的，在有效情下，支付95美元，效，支付79美元。

The firm subsequently withdrew it from the European market; it has done the same with eli-cell, which treats an irreversible nerve disease. The price it has set for Zynteglo in America is $2.8m. Some companies are getting out of the market altogether, suggesting they see no way forward.

後，公司洲市撤出此法；有治不可逆神疾病的eli-cell(是一以胞基的治候物，它使用收集自病患自身骨髓中的胞，然後在室被修改，以便它不再具有突的ABCD1基因，而是基因的作)，公司已行同置。在美，Zynteglo法已定的格是280美元。有些公司正在完全退出此市，表明它看不到前景。

Amicus Therapeutics, a biotech firm which had been working on a number of gene therapies at one point, got out of the field completely earlier this year. Within two years of having put the ADA-SCID therapy Strimvelis on the market in Europe, GSK, a big drug company, offloaded the treatment to Orchard.

在一上，一家曾一直致力於多基因法的Amicus Therapeutics生物技公司，今年(2022年)早些候，完全退出域。在腺苷氨酶-重合型免疫缺陷症法，Strimvelis法投入洲市後，年。一家大型公司，葛素史克股份有限公司(GSK：GlaxoSmithKline)法售Orchard Therapeutics公司(是一家致力於通新基因法改患者生活的生物技公司)。

If the makers are worried, so are the buyers. Health systems and insurance firms can cope with one or two such therapies at the far end of the price spectrum. Britain’s NHS, quite capable of ruling out therapies on the basis of cost, has bought both Zolgensma and Libmeldy (it negotiated a significant discount). But as the number of approved treatments grows the economics are looking more challenging.

倘若造商心，家也心。生系及保公司，能在格的端，付一或此法。英所民保健署(NHS：National Health Service)有，根成本排除多法的能力。它已收了Zolgensma及Libmeldy法(由判得了相量的折扣)。不，著批准法量的增加，因素看起更具挑性。

A study published this February by the Aspen Institute, a think-tank, and the Blue Cross Blue Shield Association, an association of American insurance companies, looked at the expected arrival of 90 gene therapies and cell therapies. By 2031 the annual acquisition cost for 550,000 patients would be $30bn.

今年(2022年)2月，由Aspen研究所(一非利的性暨智)及十字盾(美保公司所的一)，表的一，探究了期到之90基因法及胞法的研究。到2031年，55名病患每年得治的成本，是300美元。

With the country’s total prescription-drug bill currently at $577bn, that is relatively small; but it is still significant. Virtually all the buyers for health care in America have warned about the cost burden they expect as the numbers of these products grow.

管，目前方的款5770美元，相上那是小的。不，仍然不可忽。著此些品量的增加，在美所有保健的主，有他期待的用，上已出提醒。

“I think everyone agrees that the pricing of gene therapies is a crisis,” says Dr Paulk. The crisis has two main drivers: the amount of work needed to develop and make the therapies and the lack of good models for pricing one-off interventions which could obviate the need for lifelong treatment.

Paulk博士宣：「我每人皆同意，基因法的定是一危。」危有主要因素：造此些法所需的工作量，及缺乏定能避免需要身治之一次性干的良好模式。

The costs of gene therapies are not just down to arduous research and development and long-drawn-out trials. Making the material which gets put into the patient is “not for the faint of heart” says Jay Bradner, president of the Novartis Institutes for BioMedical Research. Gene therapies are “like snowflakes”, says Dr Paulk. “Every AAV program and every lot is completely unique”.

基因法的用不只於巨的研及冗的。瑞士生物研究所所，Jay Bradner表示，作置入病患的材料，是“不合怯者”。Paulk博士宣：「基因法像是雪花。每AAV程序及每一批皆是完全特的。」

Bespoke, though, does not mean small scale. She says that for diseases where you need to get the vector into a particularly large number of cells, such as Duchenne muscular dystrophy, “It is not uncommon that we need to use at least a 50 litre, if not a 200 litre, bioreactor to make a single dose for a single patient.”

不，定要求的，不意味著小模。她表示，就如杜氏肌肉萎症等，需要入大量胞的疾病而言，“需要使用至少50公升(即使不是200公升)的生物反器，一病患造次量的情，不罕”。

Analysts at the Boston Consulting Group recently estimated that the cost of manufacturing gene therapies ranges from $100,000 to $500,000 per dose. A lot of this manufacturing is done by third parties, and the difficulties of the process can be seen in the limited capacity they offer.

最近，波士集(一家美全球管理公司)的分析估算，造基因法的成本，每10美元到50美元。造很多是由第三方行，因此在他提供的有限的能耐中，能看到此程的多困。

Biotech firms that want to get into gene therapy can have to wait up to three years for manufacturing capacity to become available, according to insiders. On the other side of the coin is the difficulty of calculating benefits.

部人士的法，想入基因法域的生物技公司，了造能力成可使用，可能必需等待三年的。有值之事的另一面，是於算效益。

If a $2m treatment really does provide decades of life then the cost per year is down in the tens of thousands of dollars—hardly out of line with many other modern therapies. This has led some to suggest that payment might be in annual instalments.

倘若一次200美元的治，能提供十年的生命，那每年的用下降到美元之。多其他代法，乎不相上下。已致有些人建，付款是以年期的分期付款方式。

In the long term that could make the total larger, but it would spread it out. Another possible innovation is to couple such an approach with the option of stopping paying if the therapy stops working.

看，那使更大。不，使其分散。另一可能的新方式，是此方法倘若在治停止起作用，停止支付的相合。

The question as to whether the therapy is worth the price has to be answered in the context of what if anything the competition can offer. Take SMA, which is caused by a faulty version of a gene called smn1. Zolgensma treats this problem by providing cells with an extra copy of smn1 which works.

至於此法是否值得此格的，真正起，是在此能提供的背景下回答。以脊髓性肌萎症例，它是由一被smn1之基因，有缺陷的所引起。Zolgensma法藉由胞提供，起作用的外smn1 物，治此。

A treatment called Spinraza uses a method that increases the amount of protein made from a very similar but normally much less productive gene, smn2: its active agent is a molecule called an “antisense oligonucleotide”.

一被Spinraza法使用一，增加由非常相似，不通常很少生之基因，smn2成的蛋白量：其活性作用物是一，被“反寡核苷酸”(是短、合成、化修的核苷酸，其具有定感趣之任何基因物的力)的分子。

Antisense treatments are being tried against various conditions which look as if they can be alleviated by getting an existing gene expressed more or less. They are not permanent; Spinraza needs to be administered every four months.

多反法正各，看似能藉由使有基因或多或少作出表，而能被解的健康行。它不是永久性的；Spinraza法需要每四月被施予。

Moreover, although the cost of manufacture is far lower than for gene therapies, they are still not cheap. Biogen, the biotech company that makes Spinraza, charges up to $125,000 per dose. But such treatments may well be easier to scale up, and thus see their costs reduced.

此外，然造成本低於基因法。不，它仍然不便宜。生Spinraza法的Biogen生物技公司，每收高125千美元。不，此法或更容易大模，而降低其成本。

Haemophilia, for a form of which Roctavian, made by Biomarin, a biotech company, received EMA approval on August 24th, is another condition where alternative approaches have made huge strides, according to Dr Lillicrap.

根Lillicrap博士的法，就由Biomarin生物技公司所造，於2022年8月24日，得洲品管理局批准的一Roctavian法而言，血友病是已得巨大步之替代方法的另一疾病。

One of the newest antibodies used in its treatment needs to be given only every two to four weeks, rather than every few days, as used to be the case. Artificial versions of the clotting factors haemophiliacs cannot make have been engineered so as to last longer in the blood. There are also clever new ways of lowering the expression of proteins which suppress coagulation.

在其治中，使用的最新抗之一，需每到四周施予一次，而不是像去那，每隔天施予一次。血友病患者法造之凝血因子的人造版，已被工程改造，以便在血液中持更。降低抑制凝血之蛋白的表，也有多精巧的新方法。

It is not just what the competition can offer now that matters. It is what it might offer in five or ten years’ time. Spending a lot on a gene therapy today may prove a good investment if it provides many years of reasonably healthy life. But at the same time it is a bet against the real possibility that a cheaper and possibly better treatment is on the way.

不是那事，目前能提供什。是在五或十年中，其可能提供什。倘若基因法提供多年相健康的生活，那今天於其上的大量花，能明是一不的投。不在此同，是一行中、更便宜且可能更佳法之真正可能性的一注。

The answer to that conundrum is to make sure that gene therapies get better and cheaper, too. Various companies are looking at ways to improve manufacturing. 64x Bio, based in San Francisco, is testing millions of possible cell lines to try and find those that will grow vectors like AAV most efficiently.

那的答案是保基因法，也得更佳且更廉。各公司正在探究改善造的方法。部位於美金山的64x Bio公司，正在百可能的胞系，找那些能最有效培，像AAV的胞系。

Others are looking at the vectors themselves, trying to make them less arousing to the immune system, better targeted and more likely to actually carry the gene of interest. Current procedures leave a lot of the vectors empty; increasing the proportion that is filled would reduce dose size and costs.

其他公司正在探究本身，使它少免疫系的刺激、更佳的性及更有可能感趣的基因。前的多程序(方法)，使多空著，增加了被填少量大小及成本的比例。

Ideas for making better things to put in the vectors abound. The field started with basic tools; would-be therapists could put a gene into the genome but had little control over where it went and thus how it might be controlled and what collateral damage it might cause.

作更佳的，放入的想比比皆是。域以基本方法始；想要成的治，能一基因放入基因。不，其去哪，而如何控制它及其可能造成什伴的害，乎法控制。

In the past decade, though, great advances have been made in gene editing, a set of techniques which allow the message in an existing gene to be rewritten. As Fyodor Urnov, a professor at the University of California, Berkeley, puts it, gene therapy is like adding a fifth wheel to a car with a flat tyre; gene editing is repairing the flat.

然而，於去十年中，在基因方面，已得多重大展。是一套，使有基因中之信息得以被重的技。如同美加州大柏克分校教授，Fyodor Urnov所，基因法就像，第五子添加到有扁胎的汽；基因是在修扁平的胎。

At present, gene editing is a particularly promising route for therapies in which blood-cell-making stem cells are removed, fiddled with and reinserted into the patient’s bone marrow.

目前，基因是一，在多法方法中，造血胞遭移走、篡改，而後重新嵌入病患骨髓中，特有指望的方法。

Two clinical trials in which this sort of editing is used against sickle-cell disease, which is brought about by mutations in haemoglobin which make red blood cells deformed and defective, are already well under way. One is for a treatment from Vertex Pharmaceuticals, based in Massachusetts and CRISPR Therapeutics, the other is by bluebird bio.

在被用於抗，由血蛋白中多突，使血胞形而有缺陷所引起之胞性血症的床，已利行中。一是有自部位於美塞州Vertex Pharmaceuticals公司的法，及另一是由bluebird bio公司提供之群聚、律性隔的短文(CRISPR：Clustered Regularly Interspaced Short Palindromic Repeat)法。

More than a dozen patients are reported to have been cured, and it is possible that one of the treatments could be ready for approval next year. There are other gene therapies for the condition at earlier stages. There is also, again, competition from other approaches.

，十多名病患已被治，其中一法可能好明年得批准。在初期段，有其他供此疾病使用的基因法。此外，也有自其他方法的。

On August 8th Pfizer, another big drug company, announced its intention to acquire Global Blood Therapies, a biotech company, for $5.4bn. For that it gets Oxbryta, a drug that stops the mutant haemoglobins from sticking together, and some other therapies.

於2022年8月8日，瑞公司(另一家大型公司)宣布，其有意以54美元收Global Blood Therapies家生物技公司。此，其得 Oxbryta(一阻止突之血蛋白粘在一起的物)及一些其他法。

A similar gene-therapy approach is being used to tackle AIDS by editing into cells traits that make them immune to HIV. But here the price issue, already confounding, becomes all but lethal. Most people with AIDS, like most people with sickle-cell disease, live in low- and middle-income countries.

一藉由使胞人免疫缺陷病毒(HIV：Human Immunodeficiency Virus)具免疫力，似基因法的方法，正被用付後天性免疫缺陷症候群(AIDS：Acquired Immune Deficiency Syndrome)。不在，已令人困惑的格，得乎是致命的。大多罹患AIDS的人，大多胞性血症患者一，生活在低、中等收入家。

According to Mike McCune of the Bill & Melinda Gates Foundation, in countries where antiretroviral therapy for AIDS costs between $70 and $200 a year an all-out cure for the disease, even if it were possible, would need to come in at $2,000 or less.

根比及梅琳·茨基金Mike McCune的法，在抗逆病毒法供AIDS使用的家中，底治疾病，一年花介於70到200美元，即使有可能，也需要到2千美元或低的花。

If this sounds staggeringly unlikely, it is worth considering that there is a partial precedent. The cost of making target-specific “monoclonal” antibodies was enormous when they were first developed. But between 1998 and 2009 manufacturing improvements brought about a 50-fold reduction in the cost of goods. Matching that would allow gene therapies to move into middle-income countries, if not low-income ones.

倘若起多得人地不可能，思考有偏向一方的先例，是值得的。首度造定特性的“株”(一性繁殖系)抗，花是巨大的。不，在1998年至2009年，造上的多改善，使商品成本降低了50倍。相合，那使基因法得以入中等收入的家，倘若不是低收入的家。

As Mr Ralston can testify, gene therapies border on the miraculous. But they remain miracles of science, their creation “incredibly time-intensive [and] people-intensive,” as Dr Paulk puts it. Now they must become routinely applicable miracles of medicine.

如同Ralston先生能作那，基因法近乎能造奇。不，如同Paulk博士所，它的造“其耗[及]人密集”，仍然是科的奇。目前，它必成常用的奇。

That requires extending the range of conditions they address, learning how long they last and expanding the number of patients they help. In many ways that effort will be more demanding than the work to date.

那需要大它面的疾病，查明它持多久，及大它助的病患量。在多方面，那努力比迄今止的研究更迫切需要。

It will have to go well beyond the labs currently tinkering, the charities currently raising funds for rare diseases and the companies desperately trying to find a way to sell the remarkable things they have created. But their remarkable work has made it possible for that second miracle-making effort to begin.