Shares of Common StockPre-Funded Warrants to Purchase up toShares of Common Stock We are offeringshares of our common stock, par value $0.00001 per share, or the common stock, and, in lieu of common stock to certaininvestors that so choose, pre-funded warrants to purchase up toshares of our common stock. The purchase price of each pre-fundedwarrant will equal the price per share at which shares of our common stock are being sold to the public in this offering, minus $0.001, the exerciseprice of each pre-funded warrant. Each pre-funded warrant will be immediately exercisable for one share of common stock, subject to thelimitations described in the section “Description of the Pre-Funded Warrants—Exercisability.” The public offering price for each share of commonstock is $. We are also offering the shares of our common stock that are issuable from time to time upon exercise of the pre-funded warrants. Our common stock is listed on The Nasdaq Global Select Market under the symbol “TSHA.” The last reported sale price of our common stock onThe Nasdaq Global Select Market on June23, 2026 was $6.86 per share. There is no established public trading market for the pre-funded warrants,and we do not expect a market to develop. We do not intend to apply for listing of the pre-funded warrants on The Nasdaq Global Select Market orany securities exchange or nationally recognized trading system. Without an active trading market, the liquidity of the pre-funded warrants will belimited. We are a “smaller reporting company” under applicable Securities and Exchange Commission rules and are subject to reduced public companyreporting requirements. See “Prospectus Supplement Summary—Implications of Being a Smaller Reporting Company.” Investing in our common stock involves a high degree of risk. See “Risk Factors” beginning on page S-17 ofthis prospectus supplement, page 8 of the accompanying prospectus and under similar headings in the documentsincorporated by reference into this prospectus supplement and the accompanying prospectus. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securitiesor determined if this prospectus supplement or the accompanying prospectus is truthful or complete. Any representation to the contrary isa criminal offense. PerSharePerPre-FundedWarrantTotalPublic offering price$$$Underwriting discounts and commissions(1)$$$Proceeds to Taysha Gene Therapies, Inc., before expenses$$$ (1)See “Underwriting” for a description of the compensation payable to the underwriters. We intend to grant the underwriters an option for a period of 30 days to purchase up toadditional shares of our common stock at the initialprice to the public less the underwriting discount. The information in this preliminary prospectus supplement is not complete and may be changed. This preliminary prospectus supplement and theaccompanying prospectus are not an offer to sell the securities and are not soliciting an offer to buy the securities in any jurisdiction where the offer or sale isnot permitted.The underwriters expect to deliver the shares and pre-funded warrants against payment in New York, New York on June, 2026. PiperSandler Cantor Lead Manager Baird Prospectus Supplement dated June, 2026 Table of Contents TABLE OF CONTENTS PROSPECTUS SUPPLEMENT ABOUT THIS PROSPECTUS SUPPLEMENTSPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTSPROSPECTUS SUPPLEMENT SUMMARYTHE OFFERINGRISK FACTORSUSE OF PROCEEDSDILUTIONDESCRIPTION OF CAPITAL STOCKDESCRIPTION OF THE PRE-FUNDED WARRANTSMATERIAL U.S. FEDERAL INCOME TAX CONSEQUENCESUNDERWRITINGLEGAL MATTERSEXPERTSWHERE YOU CAN FIND MORE INFORMATIONINCORPORATION OF CERTAIN INFORMATION BY REFERENCE ABOUT THIS PROSPECTUSPROSPECTUS SUMMARYRISK FACTORSSPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS USE OF PROCEEDSDESCRIPTION OF CAPITAL STOCKDESCRIPTION OF DEBT SECURITIESDESCRIPTION OF WARRANTSLEGAL OWNERSHIP OF SECURITIESPLAN OF DISTRIBUTIONLEGAL MATTERSEXPERTSWHERE YOU CAN FIND MORE INFORMATIONINCORPORATION OF CERTAIN INFORMATION BY REFERENCE Table of Contents ABOUT THIS PROSPECTUS SUPPLEMENT This prospectus supplement is part of an automatic “shelf” registration statement on Form S-3ASR (File No.333-291244) that we filed with theSecurities and Exchange Commission, or the SEC, on November4, 2025, and which became automatically effective upon filing, as a “well-knownseasoned issuer” as defined in Rule 405 under the Securities Act of 1933, as amended, or the Securities Act, using an automatic “shelf” registrationprocess. This document is in two parts. The first part is this prospectus supplement, which describes the specific terms of this offering of common stockand pre-funded warrants and also adds to and updates information contained in the accompanying prospectus and the documents incorporated byreference herein. The second part, the accompanying prospectus, provides more general information. Generally, when we re